Function and Dysfunction of the Caveolar Network in Cell Signaling and Human Disease: An Update after 70 Years of the Discovery of Caveolae

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: 14 October 2024 | Viewed by 2996

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Department of Life Science and Public Health, Section of Histology and Embryology, Catholic University of The Sacred Heart, School of Medicine “A. Gemelli”, Largo Francesco Vito, 1 - 00168 Rome, Italy
Interests: signaling pathways; signal transduction; apoptosis; cancer biology; cell culture; PCR; inflammation; stem cell biology
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Dear Colleagues,

Caveolae (i.e., 50 to 80 nm cholesterol- and glycosphingolipid-rich, flask-shaped invaginations discovered nearly 70 years ago) have been observed in many differentiated cells. Unlike lipid rafts, whose existence remains quite elusive in living cells, caveolae are ordinarily detectable via conventional electron microscopy techniques. The unique biochemical composition of caveolae confers on them a marked resistance to solubilization by nonionic detergent, which permits the separation of these organelles from the rest of the cellular components. However, only following the discovery of the first genuine molecular marker of caveolae, i.e., caveolin-1 in the early 1990s, has the research in this field grown rapidly. Caveolin-1, encoded by the CAV gene family, is usually found coexpressed with caveolin-2 in the majority of the cell types, while the third member of the family, caveolin-3, is predominantly expressed in striated muscle cells. The ability of the caveolin scaffolding proteins to interact with a variety of signaling molecules has strongly encouraged many groups to focus on these fascinating and enigmatic structures. More than 60 years of investigation on the caveolar membrane system have strongly contributed to extending and enhancing our knowledge of the crucial cellular mechanisms, including vesicular transport, endocytosis, cholesterol homeostasis, signal transduction, cell metabolism, and cancer.  However, although the generation of caveolin knockout animals has strongly contributed to deepening the biological role of the caveolar network in vivo, many issues related to the mechanisms regulated by caveolins, both under physiological and pathological conditions, remain open. The aim of this Special Issue is to gather up-to-date results that may expand our knowledge around the multifaceted role of caveolae and caveolin proteins in cell dysfunction and human diseases. Both research and review articles related to the current state of the art in this field are also welcome.

Prof. Dr. Alessio D'Alessio
Guest Editor

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Keywords

  • cancer
  • caveolae
  • caveolin
  • cavins
  • cell metabolism
  • endocytosis
  • hypertension
  • lipid homeostasis
  • lipid rafts
  • lipodystrophy
  • mechanobiology
  • caveolinopathies
  • muscular dystrophy

Published Papers (2 papers)

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Research

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13 pages, 1923 KiB  
Article
Caveolin-1 rs1997623 Single Nucleotide Polymorphism Creates a New Binding Site for the Early B-Cell Factor 1 That Instigates Adipose Tissue CAV1 Protein Overexpression
by Ashraf Al Madhoun, Dania Haddad, Rasheeba Nizam, Lavina Miranda, Shihab Kochumon, Reeby Thomas, Thangavel Alphonse Thanaraj, Rasheed Ahmad, Milad S. Bitar and Fahd Al-Mulla
Cells 2022, 11(23), 3937; https://doi.org/10.3390/cells11233937 - 06 Dec 2022
Cited by 1 | Viewed by 1520
Abstract
Caveolin-1 (CAV1) is implicated in the pathophysiology of diabetes and obesity. Previously, we demonstrated an association between the CAV1 rs1997623 C > A variant and metabolic syndrome (MetS). Here, we decipher the functional role of rs1997623 in CAV1 gene regulation. A cohort of [...] Read more.
Caveolin-1 (CAV1) is implicated in the pathophysiology of diabetes and obesity. Previously, we demonstrated an association between the CAV1 rs1997623 C > A variant and metabolic syndrome (MetS). Here, we decipher the functional role of rs1997623 in CAV1 gene regulation. A cohort of 38 patients participated in this study. The quantitative MetS scores (siMS) of the participants were computed. CAV1 transcript and protein expression were tested in subcutaneous adipose tissue using RT-PCR and immunohistochemistry. Chromatin immunoprecipitation assays were performed using primary preadipocytes isolated from individuals with different CAV1 rs1997623 genotypes (AA, AC, and CC). The regulatory region flanking the variant was cloned into a luciferase reporter plasmid and expressed in human preadipocytes. Additional knockdown and overexpression assays were carried out. We show a significant correlation between siMS and CAV1 transcript levels and protein levels in human adipose tissue collected from an Arab cohort. We found that the CAV1 rs1997623 A allele generates a transcriptionally active locus and a new transcription factor binding site for early B-cell factor 1 (EBF1), which enhanced CAV1 expression. Our in vivo and in vitro combined study implicates, for the first time, EBF1 in regulating CAV1 expression in individuals harboring the rs1997623 C > A variant. Full article
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Review

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26 pages, 6631 KiB  
Review
Unraveling the Cave: A Seventy-Year Journey into the Caveolar Network, Cellular Signaling, and Human Disease
by Alessio D’Alessio
Cells 2023, 12(23), 2680; https://doi.org/10.3390/cells12232680 - 22 Nov 2023
Viewed by 910
Abstract
In the mid-1950s, a groundbreaking discovery revealed the fascinating presence of caveolae, referred to as flask-shaped invaginations of the plasma membrane, sparking renewed excitement in the field of cell biology. Caveolae are small, flask-shaped invaginations in the cell membrane that play crucial roles [...] Read more.
In the mid-1950s, a groundbreaking discovery revealed the fascinating presence of caveolae, referred to as flask-shaped invaginations of the plasma membrane, sparking renewed excitement in the field of cell biology. Caveolae are small, flask-shaped invaginations in the cell membrane that play crucial roles in diverse cellular processes, including endocytosis, lipid homeostasis, and signal transduction. The structural stability and functionality of these specialized membrane microdomains are attributed to the coordinated activity of scaffolding proteins, including caveolins and cavins. While caveolae and caveolins have been long appreciated for their integral roles in cellular physiology, the accumulating scientific evidence throughout the years reaffirms their association with a broad spectrum of human disorders. This review article aims to offer a thorough account of the historical advancements in caveolae research, spanning from their initial discovery to the recognition of caveolin family proteins and their intricate contributions to cellular functions. Furthermore, it will examine the consequences of a dysfunctional caveolar network in the development of human diseases. Full article
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